Cell adhesive phenomena play significant roles in hemostasis. For example, adhesion of endothelial cells to the subendothelial basement membrane is of prime importance in maintaining a barrier between circulating platelets and the basement membrane. When this barrier breaks down, adhesion of platelets to the exposed subendothelium results in thrombogenesis. The purpose of the proposed research is to explore fundamental aspects of cell biology related to cell adhesion, through the selection and characterization of cultured mammalian cell variants which possess altered adhesive properties. Specifically, we will select and study variants which are altered in their ability to attach to collagen and other inert substrata, with particular attention to native (fibrillar) collagen substrata. The selected variants will be characterized biologically, and biochemically. Biological analyses will involve observations of the cells' adhesive behavior in a variety of cell adhesion assays designed to test the ability of the cells to form initial and/or stabe attachments to, or to detach from, a specific substratum. Biochemical analyses will involve comparisons of variants and their (by definition) normally-adhering parents, with respect to protein and/or complex carbohydrate differences, using electrophoretic, chromatographic, and immunological methods. The ultimate aim of these studies is to identify specific molecules which function in cell adhesion.